This proposal requests funds to examine allostatic load as a potential mechanism in the development of depression in Mexican-origin adolescents. Allostatic load is the loss of flexibility in how physiological systems respond to stressful experiences. High levels of allostatic load have been identified in Mexican origin adults who experience economic, familial, workload, and acculturative stress, yet allostatic load has not been examined from a dynamic, multi-systemic or longitudinal perspective in this ethnic group. Because adolescence increases the risk for the development of depression, longitudinal data are needed to understand how allostatic load and depression change over time in Mexican-origin youth, who 1) are among the largest ethnic minority group in the US, 2) face high risk for depression, and 3) experience high levels of stress. A comprehensive assessment of dynamic, multi-systemic neurobiological reactivity to incentives and social stressors, two symptom-specific contexts, is proposed to assess allostatic load. Our proposed study will add these assessments to an existing, ongoing longitudinal study of the development of psychopathology and adjustment in 673 adolescents of Mexican origin (California Families Project [CFP]; 2R01DA017902-06; Contact PI: R. Conger). From this larger sample, we will identify 250 youths (50% female) with elevated risk for depression based on symptom counts and neuroticism at age 15 years. At ages 16 and 18 years, these selected youth will complete functional magnetic resonance imaging scans while adrenocortical, immunological and autonomic psychophysiological data are collected simultaneously. We expect that high neurobiological reactivity to social stressors and low reactivity to incentives will relate to high levels of depression symptoms in Mexican-origin adolescents. We also hypothesize that neurobiological reactivity will be a more effective index of allostatic load in adolescence than a more traditional additive measure of allostatic load using elevated static measures of physiology. Importantly, by integrating the proposed study and the existing CFP study, we will capitalize on the extensive available data on risk and protective factors (e.g., cognitive, personality, behavioral, contextual and cultural) offered by the CFP. These data on risk and protective factors will support proposed analyses based on biopsychosocial models of the development of depression in Mexican-origin adolescents. We will examine allostatic load as a mediator and a moderator of associations among risk and protective social-contextual factors and changes in depression. Results of the study are expected to inform the development of more effective and culturally sensitive prevention programs for an important, growing and understudied population. The existence of the ongoing CFP study (through 2015) by Dr. Conger and colleagues, with a committed and representative community sample of Mexican origin families, makes this proposal feasible. The timing of the proposal is critical, as youths will be 16 years old when the start of neurobiologica data collection is planned. Consequently, this will be one of the only prospective longitudinal studies of allostatic load as a mechanism of the development of depression in Mexican-origin adolescents.